Three-dimensional structure of recombinant human interferon-gamma

Abstract

The x-ray crystal structure of recombinant human interferon-gamma has been determined with the use of multiple-isomorphous-replacement techniques. Interferon-gamma, which is dimeric in solution, crystallizes with two dimers related by a noncrystallographic twofold axis in the asymmetric unit. The protein is primarily alpha helical, with six helices in each subunit that comprise approximately 62 percent of the structure; there is no beta sheet. The dimeric structure of human interferon-gamma is stabilized by the intertwining of helices across the subunit interface with multiple intersubunit interactions.

Interleukin‐6: Structure‐function relationships

“…McKay, 1992 Feng et al, 1996Redfield et al, 1994Powers et al, 1992, 1993Muller et al, 1994Walter et al, 1992aWlodawer et al, 1992Muller et al, 1995Walter et al, 1992bRozwarski et al, 1996Milburn et al, 1993Pandit et al, 1992Hill et al, 1993Zink et al, 1994Lovejoy et al, 1993Lovejoy et al, 1993Lovejoy et al, 1993Robinson et al, 1994de Vos et al, 1992Ultsch et al, 1994Somers et al, 1994Sundstrom et al, 1996Sundstrom et al, 1996 Chantalat et aLc Abdel-Meguid et al, 1987McDonald et al, 1995Walter & Nagahhushan, 1995Zdanov et al, 1996Radhakrishnan et al, 1996Senda et al, 1995Ealick et al, 1991Samudzi et al, 1991Samudzi & Rubin, 1993Livnah et al, 1996de Vos et al, 1992Sundstrom et al, 1996Sundstrom et al, 1996Somers et al, 1994Harlos et al, 1994Muller et al, 1996Banner et al. 1996 "Cytokine or receptor class is shown along with the method of structure determination and resolution where appropriate.…”

Hematopoietic cytokines: Similarities and differences in the structures, with implications for receptor binding

“…(Senda et al, 1992), and interferon-y is a tight dimer in which each chain contains six helices. The helices that form the equivalent of the four-helix bundles discussed above come from both chains (Ealick et al, 1991;Samudzi et al, 1991).…”

Structure and function of interleukin-22 and other members of the interleukin-10 family

“…b A phylogram tree extract from this alignment. Alignment was performed using ClustalW [170] IL-10 Helix F2 to C-term [23] IFN-k1 b 34,68,131,164,190 Probably similar to IFN-k3, with the exception of interaction #3 [23] observed in IL-19, IL-22, and IFN-k3 crystal structures (Fig. 2b).…”

“…Each IL-10 subunit has two disulfide bonds connecting the DE loop to helix C (Cys62-Cys114) and to the N-terminal region (Cys12-Cys108). These S-S interactions, mainly the one between Cys62 and Cys114, promote a certain degree of rigidity of helix E. As a consequence, helices E and F fold as an independent IL-10 domain that makes a right angle with the other domain composed of helices A-D [6,7,130,131]. This promotes two IL-10 polypeptide chains to join together to form an intertwined V-shaped dimer.…”

“…2a). In IFN-c, a short DE loop is the main reason for a similar structural architecture; however, in IFN-c, the angle formed between the two monomers is *60° [131][132][133][134]. In IL-10, the 90°inter-domain angle allows helix C to be exposed, creating a potential interaction site with its receptors [6].…”